Summary

Subjects

22,748 pregnant women originally recruited 1984-1987 for a study evaluating
risk factors for neural-tube defects and enrolled mainly between weeks
15-20 of pregnancy (at time of plasma AFP measurement or amniocentesis).

Data on diet, dietary retinol intake and vitamin supplements were collected
by telephone questionnaire, data on pregnancy outcome by questionnaires
sent to obstetricians (77%) and mothers (23%) after delivery. For this
study, defects were classified as: cranial-neural-crest (craniofacial,
CNS except neural tube, thymic and heart), neural tube, musculoskeletal/urogenital,
and other (GI and non-GI).

Results

Among the 22,748 women, there were 339 births with birth defects, 121
of cranial-neural-crest origin. The prevalence of cranial-neural-crest
defects among the 500 women who consumed >15,000 IU of retinol daily (dietary
plus supplements) was 1.8%, compared with 0.51% among the 6410 women who
consumed <5,000 IU (relative risk of 3.5). Looking at retinol from supplements
alone, the prevalence of cranial-neural-crest defects among the 317 women
consuming >10,000 IU daily was 2.21% vs. 0.46% among the 11,083 consuming
< 5,000 IU daily (relative risk 4.8).

Dose-response curves suggested a threshold value of about 10,000 IU
daily. Subgroup analysis suggests main effect occuring before week 7 of
pregnancy. Consumption of over 10,000 IU of vitamin A daily would be expected
to lead to a birth defect in one of every 57 births.

Comment

In an accompanying editorial G. Oakley and J. Erickson from the CDC point
out that the potential toxicity from vitamin A should not be confused with
the protective effect from folate (demonstrated from earlier results of
this same study). They also feel that this study is well suited to show
the safety of vitamin A intake below 10,000 IU daily. Whether the actual
threshhold for increased risk is actually 10,000 is less sure, but prudence
dictates recommending a multivitamin supplement with less than 8,000 IU
of vitamin A and limiting the intake of liver and liver products.